CHICAGOâ€”Two posters presented at the 2015 ASCO Annual Meeting provided encouraging data for the use of the pi3k delta inhibitor idelalisib in the treatment of chronic lymphocytic leukemia (CLL) and follicular lymphoma (FL).
In the first study, Jeffrey Alan Jones, MD, MPH, assistant professor of internal medicine at the Ohio State University Wexner Medical Center in Columbus, Ohio, and colleagues examined the safety and efficacy of a combination of idelalisib and ofatumumab – versus ofatumumab alone – in the treatment of CLL.
Dr. Jones and investigators enrolled more than 250 patients with CLL whose disease had progressed in the 24 months or less from their last therapy. Patients were randomized 2:1 to receive 150 mg idelalisib orally twice-daily continuously plus ofatumumab (n=173) or ofatumumab alone (n=86).
Adding idelalisib to the treatment regimen increased the median progression-free survival (PFS): 16.3 months for patients receiving the combination therapy, compared with eight months for the single-therapy cohort (HR=0.27; p<0.0001).
Rates of grade â‰¥3 treatment-related adverse events for patients receiving idelalisib included diarrhea/colitis (20.2%), pneumonia (12.7%), and febrile neutropenia (11.6%).
Overall, the researchers concluded, idelalisib plus ofatumumab yielded superior PFS, including within high-risk subgroups (TABLE).
|TABLE. Efficacy outcomes with combination or monotherapy|
Idelalisib + ofatumumab
|Ofatumumab(n=86)||Hazard ratio/Odds ratio|
|Median progression-free survival, months||16.3||8.0||HR=0.27 (p<0.0001)|
|Overall response rate, %||75.3||18.4||OR=15.9 (p<0.0001)|
|Lymph node response, %||93.3||4.9||OR=4.87 (p<0.0001)|
|Median overall survival, months||20.9||19.4||HR=0.74 (p=0.27)|
|Median progression-free survival in high-risk patients ([del[17p, TP53 mutation), months||13.7||5.8||HR=0.33 (p<0.0001)|
In the second study, Gilles A. Salles, MD, PhD, from the Hospices Civils de Lyon, UniversitÃ© Claude Bernard in Pierre BÃ©nite, France, and colleagues examined idelalisib as a treatment option for follicular lymphoma – a disease with few treatment options, particularly for heavily pretreated, high-risk patients refractory to anti-CD20 and chemotherapy.
This phase II study was a post-hoc analysis of a pivotal, phase II, open-label study on idelalisib. Double-refractory patients with histologically confirmed indolent non-Hodgkin lymphoma received 150 mg idelalisib orally twice-daily until disease progression or unacceptable tolerability. Of the patients, 72 had grade 1, 2, or 3a follicular lymphoma. The median number of prior treatment was four, with 86 percent of patients refractory to their last therapy. At the data cutoff point, the median treatment duration was 6.5 months, with 90 percent of patients off treatment.
The researchers noted an overall response rate of 56 percent for idelalisib-treated patients (95% CI 43-67; p<0.001), including 10 complete responses and 30 partial responses. Median time to response was 2.6 months, and Dr. Salles and investigators also found that the responses were durable: median response duration was 11 months and median overall survival was not reached at the time of the presentation.
The most common grade â‰¥3 treatment-related adverse events again included diarrhea, cough, pyrexia, fatigue, and nausea.
Ultimately, the researchers concluded that "idelalisib demonstrated rapid, durable responses and acceptable safety in highly refractory, relapsed follicular lymphoma patients with limited treatment options."
- Jones JA, Wach M, Robak T, et al. Results of a phase III randomized, controlled study evaluating the efficacy and safety of idelalisib (IDELA) in combination with ofatumumab (OFA) for previously treated chronic lymphocytic leukemia (CLL). Abstract #7023. Presented at the American Society of Clinical Oncology Annual Meeting, Chicago, Illinois, May 31, 2015.
- Salles GA, Schuster SJ, De Vos S et al. Idelalisib efficacy and safety in follicular lymphoma patients from a phase 2 study. Abstract #8529. Presented at the 2015 American Society of Clinical Oncology Annual Meeting, Chicago, Illinois, May 31, 2015.